Comments on the letter by Ribeiro et al.: Impairment of parasympathetic-mediated autonomic modulation of the heart in Chagas' cardiomyopathy: Parasympathetic modulation vs. tonus

Benchimol-Barbosa, Paulo Roberto

doi:10.1016/j.ijcard.2008.01.019

Cited by 4 publications

(3 citation statements)

References 10 publications

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“…We read with great interest the text of Benchimol-Barbosa [1] about our letter, [2] in which we stated that although cardiac vagal impairment has been repeatedly demonstrated in Chagas disease (ChD), in vivo detection of vagal enhancement was still lacking. Benchimol-Barbosa elegantly hypothesized that a continuous effect of anti-muscarinic antibody acting on sinus node M2 receptors would both steadily hold heart rate at a lower level and limit acute heart rate variations secondary to oscillation in spontaneous neural parasympathetic efferent.…”

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confidence: 99%

Enhanced parasympathetic activity in Chagas disease still stands in need of proof

Ribeiro

Carvalho

Lombardi

et al. 2009

International Journal of Cardiology

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Cardiac vagal modulation impairment is a typical feature of Chagas disease (ChD) and is correlated to antagonistic anti-M2 autoantibodies activity. In this letter, we analyze the hypothesis that, in ChD, anti-muscarinic antibody activity could simultaneously increase parasympathetic tonus (decreasing heart rate) and decrease vagal modulation over cardiac sinus node (reducing heart rate variability — HRV). Although attractive, this hypothesis is not supported by empirical data, since reduction of vagal-specific HRV indexes has been demonstrated in the absence of bradycardia. Moreover, anti-muscarinic antibody levels correlate with HRV indexes, but not with heart rate. In the absence of reduced heart rate and, consequently, of tonic vagal enhancement, it is impossible to explain the reduction of vagal-mediated HRV by continuous and strong muscarinic activity of autoantibodies in ChD.

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confidence: 99%

Enhanced parasympathetic activity in Chagas disease still stands in need of proof

Ribeiro

Carvalho

Lombardi

et al. 2009

International Journal of Cardiology

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“…Since, muscarinic auto-antibodies may behave as positive allosteric modulators of parasympathetic activity 25 ; a diminished high frequency component of heart rate variability 41 and the presence of a slow heart rate 44 could be an indirect expression of the agonist effect. Thus, an alternative explanation for the "impaired" chronotropic response to the cardiac autonomic tests would be over stimulation with saturation of the parasympathetic system 3,11,12,42 . Indeed, as stated by BENCHIMOL-BARBOSA a continuous cholinergic effect of anti-M2 antibody, by acting on the muscarinic receptor of the sinus node cells, could slow heart rate and limit acute heart rate variations.…”

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confidence: 99%

“…Indeed, as stated by BENCHIMOL-BARBOSA a continuous cholinergic effect of anti-M2 antibody, by acting on the muscarinic receptor of the sinus node cells, could slow heart rate and limit acute heart rate variations. Therefore, adjustments of heart rate in response parasympathetic efferent activity are expected to be apparently "impaired" 3 . Consequently, we have studied the cardiac 32 chronotropic responses to the Valsalva maneuver and to dynamic exercise and correlated them with the serum levels of cardiac muscarinic auto-antibodies, of chagasic patients who were in the indeterminate form of the disease.…”

Section: Introductionmentioning

confidence: 99%

Muscarinic antibodies and heart rate responses to dynamic exercise and to the Valsalva maneuver in chronic chagasic patients

Neves¹,

Bacilio²,

Berrueta

et al. 2013

Rev. Inst. Med. trop. S. Paulo

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SUMMARYWe have studied the cardiac chronotropic responses to the Valsalva maneuver and to dynamic exercise of twenty chronic chagasic patients with normal left ventricular function and no segmental wall abnormalities by two-dimensional echocardiogram. The absolute increase in heart rate of the patients (∆ = 21.5 ± 10 bpm, M±SD) during the maneuver was significantly diminished when compared to controls (∆ = 31.30 ± 70, M±SD, p = 0.03). The minimum heart rate (58.24 ± 8.90 vs. 62.80 ± 10, p = 0.68) and the absolute decrease in heart rate at the end of the maneuver (∆ = 38.30 ± 13 vs. ∆ = 31.47 ± 17, p = 0.10) were not different from controls. The initial heart rate acceleration during dynamic exercise (∆ = 12 ± 7.55 vs. ∆ = 19 ± 7.27, M±SD, p = 0.01) was also diminished, but the heart rate recovery during the first ten seconds was more prominent in the sero-positive patients (Median: 14, Interquartile range: (9.75-17.50 vs. 5(0-8.75, p = 0.001). The serum levels of muscarinic cardiac auto-antibodies were significantly higher in the chagasic patients (Median: 34.58, Interquartile Range: 17-46.5, Optical Density) than in controls (Median: 0, Interquartile Range: 0-22.25, p = 0.001) and correlated significantly and directly (r = 0.68, p = 0.002) with early heart rate recovery during dynamic exercise. The results of this investigation indirectly suggest that, the cardiac muscarinic auto-antibodies may have positive agonist effects on parasympathetic heart rate control of chagasic patients.

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Comments on the article by Ribeiro et al. ‘Enhanced parasympathetic activity in Chagas' disease still stands in need of proof’: Definitions and biases

Benchimol-Barbosa

2011

International Journal of Cardiology

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It has been hypothesized that impaired cardiac autonomic function in chagasic subject carriers of anti-muscarinic type 2 antibodies (Anti-M2) is a consequence of tonic stimulation (enhancement) of M2 receptors, thus damping high frequency spontaneous heart rate fluctuations. However, expected reduction in baseline average heart rate response as a consequence of M2 receptors stimulation has not been confirmed, imposing a query on current hypothesis for explaining autonomic impairment in Chagas' disease. In this context, possible explanations for the lack of heart rate reduction in the setting of chronic muscarinic stimulation in Chagas' disease have been discussed, based on current knowledge. Among possible factors implicated, stands out: i) spontaneous heart rate recovery after chronic vagal stimulation, ii) simultaneous anti-M2 and anti-beta 1 adrenergic receptors antibodies environments, iii) underlying cardiac function as assessed by both mechanical and humoral indexes, iv) age, v) immune status. Rigorous experimental settings may be necessary to mechanistically demonstrate eventually the association between agonistic anti-M2 environments and reduced autonomic modulation of the heart, in both humans and animal models, associated with short term and long term singular average resting heart rate balance secondary to parasympathetic stimulation.

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Comments on the letter by Ribeiro et al.: Impairment of parasympathetic-mediated autonomic modulation of the heart in Chagas' cardiomyopathy: Parasympathetic modulation vs. tonus

Cited by 4 publications

References 10 publications

Enhanced parasympathetic activity in Chagas disease still stands in need of proof

Enhanced parasympathetic activity in Chagas disease still stands in need of proof

Muscarinic antibodies and heart rate responses to dynamic exercise and to the Valsalva maneuver in chronic chagasic patients

Comments on the article by Ribeiro et al. ‘Enhanced parasympathetic activity in Chagas' disease still stands in need of proof’: Definitions and biases

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